Kuriyama Genshin, Takekoshi Susumu, Tojo Katsuyoshi, Nakai Yoshikatsu, Kuhar Michael J, Osamura R Yoshiyuki
Department of Pathology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
Endocrinology. 2004 May;145(5):2542-50. doi: 10.1210/en.2003-0845. Epub 2004 Feb 5.
Cocaine- and amphetamine-regulated transcript (CART) mRNA and CART peptide are abundant in the hypothalamic nuclei that control anterior pituitary function. CART peptide has also been localized in the anterior pituitary gland itself, although its role in pituitary function has not as yet been elucidated. In the present study, we investigated the localization and function of CART peptide in the anterior pituitary gland. Immunohistochemical observations revealed that CART peptide colocalized with FSH and LH in gonadotroph cells but that it was absent from the other hormone-producing cells. Immunoelectronmicroscopy suggested that CART peptide and gonadotropin were colocalized in the same secretory granules. CART peptide suppressed prolactin release from dispersed anterior pituitary cells 15 min after its addition into the media [basal production, 234.9 +/- 14.6 ng/ml vs. CART 55-102 peptide 100 nm, 125.0 +/- 18.2 ng/ml (P < 0.01, n = 5)]. Prolactin release was suppressed by CART in a dose-related manner; on the other hand, CART peptide did not affect the secretion of other anterior pituitary hormones. CART peptide synthesis by these cells was elevated 15 min after the addition of leptin to the media (100 nm), as determined by immunoblotting, but LHRH (10 nm) did not significantly affect CART peptide expression. These findings suggest that CART synthesis in the anterior pituitary may be stimulated by leptin and that CART peptide may play a role in the regulation of anterior pituitary hormone secretion in the rat.
可卡因和苯丙胺调节转录物（CART）mRNA及CART肽在下丘脑控制垂体前叶功能的核团中含量丰富。CART肽也已定位在垂体前叶本身，尽管其在垂体功能中的作用尚未阐明。在本研究中，我们调查了CART肽在垂体前叶中的定位和功能。免疫组织化学观察显示，CART肽在促性腺激素细胞中与促卵泡激素（FSH）和促黄体生成素（LH）共定位，但在其他激素分泌细胞中不存在。免疫电子显微镜检查表明，CART肽和促性腺激素共定位在相同的分泌颗粒中。将CART肽加入培养基15分钟后，其抑制了分散的垂体前叶细胞催乳素的释放[基础分泌量，234.9±14.6 ng/ml vs. CART 55 - 102肽100 nM，125.0±18.2 ng/ml（P < 0.01，n = 5）]。CART以剂量相关的方式抑制催乳素释放；另一方面，CART肽不影响垂体前叶其他激素的分泌。通过免疫印迹法测定，在培养基中加入瘦素（100 nM）15分钟后，这些细胞的CART肽合成增加，但促性腺激素释放激素（LHRH，10 nM）对CART肽表达无显著影响。这些发现表明，垂体前叶中的CART合成可能受瘦素刺激，并且CART肽可能在大鼠垂体前叶激素分泌的调节中发挥作用。
